Wu, X.; Zang, R.; Zhang, C.; Liu, M.; Wei, S.; Yang, N.; Wang, S.; Diao, Y. Baicalein Attenuates Myocardial Fibrosis via Directly Targeting Phosphoglycerate Mutase 1. Preprints2024, 2024050496. https://doi.org/10.20944/preprints202405.0496.v1
APA Style
Wu, X., Zang, R., Zhang, C., Liu, M., Wei, S., Yang, N., Wang, S., & Diao, Y. (2024). Baicalein Attenuates Myocardial Fibrosis via Directly Targeting Phosphoglycerate Mutase 1. Preprints. https://doi.org/10.20944/preprints202405.0496.v1
Chicago/Turabian Style
Wu, X., Siqi Wang and Yong Diao. 2024 "Baicalein Attenuates Myocardial Fibrosis via Directly Targeting Phosphoglycerate Mutase 1" Preprints. https://doi.org/10.20944/preprints202405.0496.v1
Abstract
Myocardial fibrosis is a pivotal pathophysiological step of various cardiovascular diseases, which eventually leads to heart failure and death. Cardiac fibroblasts activation and subsequently differentiate into myofibroblasts are pivotal pathophysiological step in myocardial fibrosis. Phosphoglycerate mutase 1 (PGAM1) directly interacts with α-smooth muscle actin (ACTA2) and participate in fibrosis regulation. Allosteric inhibitor of PGAM1 could attenuates fibrosis through break the interaction of PGAM1 and ACTA2. In this study, we aimed to screen and identify novel ligand of PGAM1 in natural product library. Firstly, various natural products were screened via DARTS assay and Carthamus tinctorius L. was identified as a target pool for molecular docking. Then, in silico screening assay identified baicalein as a novel ligand. In addition, baicalein could directly bind to the PGAM1 protein with a KD value of 34.6 μM. Molecular dynamics simulation revealed that baicalin and PGAM1 interactions were stable. These findings indicate that PGAM1 is a direct pharmacological target of baicalein. Immunoblot analysis further demonstrated that baicalin inhibits the activation of fibroblasts in vitro. Finally, the anti-myocardial fibrosis effect of baicalein was verified in vivo. Taken together, our findings suggest that baicalein is a novel PGAM1 templates for developing new therapeutics against myocardial fibrosis.
Keywords
DARTS; Myocardial fibrosis; PGAM1; Baicalein; Carthamus tinctorius L.
Subject
Medicine and Pharmacology, Medicine and Pharmacology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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